PATHOGENIC AND ADAPTIVE MOLECULAR INTERACTIONS WITH MUTANT HUNTINGTIN EXON 1
Grant number: 1102059 | Funding period: 2016 - 2019
This project aims to determine how the gene mutation that causes Huntington’s disease (HD) damages cells in the brain. The diseased gene creates a protein that is abnormally sticky, which causes it to form clumps. Our goal is to determine the components of the cell that are disrupted and damaged as clumping happens. Understanding this link will enable therapeutics to be logically designed in efforts to prevent harm to the brain, potentially before symptoms are evident.
Related publications (7)
Nascent mutant Huntingtin exon 1 chains do not stall on ribosomes during translation but aggregates do recruit machinery involved in ribosome quality control and RNA
Angelique R Ormsby, Dezerae Cox, James Daly, David Priest, Elizabeth Hinde, Danny M Hatters
Mutations that cause Huntington's Disease involve a polyglutamine (polyQ) sequence expansion beyond 35 repeats in exon 1 of Huntin..
A thiol probe for measuring unfolded protein load and proteostasis in cells
Moore Z Chen, Nagaraj S Moily, Jessica L Bridgford, Rebecca J Wood, Mona Radwan, Trevor A Smith, Zhegang Song, Ben Zhong Tang, Leann Tilley, Xiaohong Xu, Gavin E Reid, Mahmoud A Pouladi, Yuning Hong, Danny M Hatters
When proteostasis becomes unbalanced, unfolded proteins can accumulate and aggregate. Here we report that the dye, tetraphenylethe..
Transcriptional profiles for distinct aggregation states of mutant Huntingtin exon 1 protein unmask new Huntington's disease pathways
Nagaraj S Moily, Angelique R Ormsby, Aleksandar Stojilovic, Yasmin M Ramdzan, Jeannine Diesch, Ross D Hannan, Michelle S Zajac, Anthony J Hannan, Alicia Oshlack, Danny M Hatters
Huntington's disease is caused by polyglutamine (polyQ)-expansion mutations in the CAG tandem repeat of the Huntingtin gene. The c..
Conformational dynamics and self-association of intrinsically disordered Huntingtin exon 1 in cells
Steffen Buening, Abhishek Sharma, Shivang Vachharajani, Estella Newcombe, Angelique Ormsby, Mimi Gao, David Gnutt, Tobias Voepel, Danny M Hatters, Simon Ebbinghaus
Huntington's disease is caused by a CAG trinucleotide expansion mutation in the Huntingtin gene that leads to an artificially long..
Huntingtin Inclusions Trigger Cellular Quiescence, Deactivate Apoptosis, and Lead to Delayed Necrosis
Yasmin M Ramdzan, Mikhail M Trubetskov, Angelique R Ormsby, Estella A Newcombe, Xiaojing Sui, Mark J Tobin, Marie N Bongiovanni, Sally L Gras, Grant Dewson, Jason ML Miller, Steven Finkbeiner, Nagaraj S Moily, Jonathan Niclis, Clare L Parish, Anthony W Purcell, Michael J Baker, Jacqueline A Wilce, Saboora Waris, Diana Stojanovski, Till Bocking
Competing models exist in the literature for the relationship between mutant Huntingtin exon 1 (Httex1) inclusion formation and to..
N-Terminal Fragments of Huntingtin Longer than Residue 170 form Visible Aggregates Independently to Polyglutamine Expansion
Moore Z Chen, Sue-Ann Mok, Angelique R Ormsby, Paul J Muchowski, Danny M Hatters
BACKGROUND: A hallmark of Huntington's disease is the progressive aggregation of full length and N-terminal fragments of polygluta..